We are requesting funding for a state-of-the-art matrix-assisted laser desorption ionization time-of-flight/time- of-flight (MALDI-TOF/TOF) mass spectrometer to be utilized for imaging by mass spectrometry (ImMS) of thin tissue sections. An exciting new application of proteomics technology is molecular imaging of tissues by MALDI-TOF/TOF mass spectrometry (MS). Direct tissue profiling and imaging mass spectrometry provide a detailed assessment of the complex protein pattern within a tissue sample, allows visualization of the spatial distribution of proteins/peptides and other analytes in tissue sections, and insight into specific cell and tissue biology and pathology. This newly developed technique requires high sensitivity mass spectrometry and we will be taking advantage of the ability of the mass spectrometer to operate in both linear mode for sensitivity and reflectron mode for high resolution and mass accuracy. The MS/MS sequencing capabilities of the instrument will allow the identification of clinically relevant peptides directly from the tissues without further fractionation or isolation. Tissue imaging by MALDI allows for automated processing of clinical specimens in a high-throughput fashion and expands the research capacity of the Clinical Proteomics Core, the Tissue Procurement Core Laboratory, and the Molecular Instrumentation Center at UCLA. The MALDI-TOF/TOF imaging system will be an important part of over 10 different NIH-funded projects at UCLA. The funded research will impact a number of biomedically-oriented studies including cancer (prostate, brain, skin, and lung cancers), immune/inflammatory disorders (inflammatory bowel disease), metabolic disease (diabetes and metabolic syndrome), and cardiovascular disease (atherosclerosis). PUBLIC HEALTH RELEVANCE: The new instrumentation will benefit a wide range of clinically-oriented studies, particularly in the field of translational medicine. We will be seeking new biomarkers in an array of important human conditions including prostate and lung cancer, glioblastoma, melanoma, and inflammatory bowel disease. Our studies will seek both to identify new biomarker candidates as well as to better understand the etiology and pathology of disease progression.